Comparative study of inorganic, boron-rich cluster and organic, phenyl adenosine modifications: synthesis and properties

• Published in: Future medicinal chemistry 2019-06, Vol.11 (11), p.1267-1284
• Main Authors: Mieczkowski, Adam, Kierozalska, Aleksandra, Białek-Pietras, Magdalena, Goszczyński, Tomasz M, Janczak, Sławomir, Olejniczak, Agnieszka B, Studzińska, Mirosława, Paradowska, Edyta, Leśnikowski, Zbigniew J
• Format: Article
• Language: English
• Subjects: adenosine; Adenosine - analogs & derivatives; Adenosine - chemical synthesis; Adenosine - pharmacology; Animals; antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; boron clusters; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Boron Compounds - pharmacology; Chlorocebus aethiops; circular dichroism; conjugates; cytotoxicity; drug design; enzymatic phosphorylation; Humans; lipophilicity; nucleosides; Vero Cells; Virus Diseases - drug therapy; Viruses - drug effects
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2018-0517

Nucleoside analogs are important class of chemotherapeutics. One of the original openings in the nucleoside medicinal chemistry was derivatives comprising a boron cluster component. A series of adenosine derivative pairs containing inorganic boron cluster or alternatively its mimic, organic phenyl modification were synthesized and their physicochemical and biological properties compared. Marked effects of boron clusters, which are qualitatively and quantitatively different from the phenyl group effects, were detected. The studied characteristics include / conformation, lipophilicity, cytotoxicity and antiviral activity, as well as phosphorylation by adenosine kinase. The obtained results demonstrate usefulness of the boron clusters for tuning properties of biomolecules and prove their potential as modifying units in design of future therapeutics based on nucleoside structures.